Antiulcer agent

ABSTRACT

The present invention provides antiulcer agents which can be orally administered while producing few side effects. These antiulcer agents contain α-lactalbumin as an active ingredient, preferably in an amount of at least 0.5 mg/g.

TECHNICAL FIELD

The present invention relates to an antiulcer agent. More specifically,the present invention relates to an antiulcer agent, includingα-lactalbumin as an active ingredient, which produces no side effects.

BACKGROUND ART

An ulcer (a peptic ulcer) is tissue damage resulting from necrosis to acertain depth of skin or mucous membrane in the esophagus, stomach, orduodenum, which is directly caused by hydrochloric acid or pepsin ingastric juice induced by stress, alcohol, a nonsteroidalanti-inflammatory drug (NSAID) such as indomethacin, or the like.

Specific examples of the antiulcer agent used for treatment of ulcersinclude an antacid which can neutralize gastric acid, and ananticholinergic drug, an H₂ blocker, a proton pump inhibitor, and thelike, which can suppress secretion of gastric acid.

Although specific examples of the antacids include sodiumhydrogencarbonate, magnesium carbonate, aluminium hydroxide, and amixture thereof, these have various problems. For example, they must betaken at frequent intervals because of the short duration of the actionthereof, and the laxative action of the formulation is strong when itincludes magnesium (Journal of Medicine, volume 27, page 2272, 1991).

Conventional anticholinergic drugs and H₂ blockers (such as cimetidine)are known to have various problems. For example, the acute toxiciticdose thereof is low, side effects are caused by the binding thereof torespective receptors somewhere other than lesions (for example,cimetidine is known to cause hematologic disorders, hepatic disorders,renal disorders, endocrine disorders, mental or nervous disorders,digestive disorders, and hypersensitivity), and interference with otherdrugs occurs (Journal of Medicine, volume 27, page 2272, 1991; and DRUGSin JAPAN edited by the Japan Pharmaceutical Information Center, JihoInc., page 517, 1993).

Conventional proton pump inhibitors also have problems such as thegeneration of carotenoids (Journal of Medicine, volume 27, page 2272,1991).

In contrast, specific examples of the antiulcer agents containing aprotein, or a peptide as an active ingredient, include secretin,somatostatin, calcitonin, urogastrone, and the like.

Moreover, specific examples of a formulation derived from whey includemethanol extract of whey (Japanese Unexamined Patent Application, FirstPublication No. Sho 62-277327, which is referred hereinafter to as PriorArt 1), whey protein (Japanese Unexamined Patent Application, FirstPublication No. Hei 1-268644, which is referred hereinafter to as PriorArt 2), and whey protein degradation product which is hydrolyzed by anenzyme (Japanese Unexamined Patent Application, First Publication No.Sho 56-32488, which is referred hereinafter to as Prior Art 3).

The peptide formulation, such as secretin, somatostatin, or calcitoninhas a problem in that it is required to be administered by injection,which is accompanied by pain, and continuous administration is difficult(Journal of Medicine, volume 27, page 2272, 1991).

Although urogastrone is a peptide formulation for oral administration,it has problems in that the amount of urogastrone which can be preparedis limited, and in that the cost required for preparing urogastrone ishigh because the raw material from which urogastrone is prepared bypurification is pregnant mare urine. Moreover, administration ofurogastrone tends to cause side effects such as thirst, nausea,discomfort in the gastric region, diarrhea, constipation, and/or thelike (DRUGS in JAPAN edited by the Japan Pharmaceutical InformationCenter, Jiho Inc., page 517, 1993).

Moreover, the methanol extract of whey (Prior Art 1) has a problem inthat it is difficult to be used as a food material, because methanol isunsuitable in view of food safety, and the antiulcer substances preparedfrom other wheys (Prior Arts 2 and 3) have a problem in that theantiulcer action thereof is insufficient.

Therefore, antiulcer agents having neither the problems described abovenor the side effects described above are awaited.

α-lactalbumin is known to be a globular protein which accounts forapproximately 25% (weight percent; the same units below unlessspecifically mentioned otherwise) of whey protein and has a molecularweight of approximately 14,100, and to play a part in a synthesis oflactose (“Comprehensive Encyclopedia of Milk” edited by Kunio Yamauchiand Kenkichi Yokoyama, Asakura-Shyoten Co., Ltd., page 35, 1992).Moreover, α-lactalbumin is known to have a gelation property and to beincluded in foods for masking effects or quality improvement, as well asin albumen substitutes, kneaded foods, or the like (“'94 The Present andthe Future of Protein and Peptide Foods”, Seed * Planning Co., Ltd.,page 37, 1994).

However, α-lactalbumin is not known to have strong antiulcer action, andthis is not disclosed in any literature.

As is obvious from the prior art described above, although antiulceragents for oral administration having few side effects are awaited,substances have not yet been discovered having superior effects.

DISCLOSURE OF INVENTION

As a result of extensive research aimed at obtaining more effectiveantiulcer agents, the inventors of the present invention discovered thatα-lactalbumin has antiulcer effects in vivo, and have thereby completedthe present invention.

The present invention was made in view of the circumstances describedabove, and an object of the present invention is to provide an antiulceragent, for oral administration, which produces few side effects.

The present invention, which can overcome the problems described above,is an antiulcer agent including α-lactalbumin as an active ingredient,wherein α-lactalbumin is preferably included in an amount of at least0.5 mg per 1 g of the antiulcer agent. Moreover, α-lactalbumin is morepreferably included as an active ingredient in an amount of 1 mg per 1 gof the antiulcer agent.

BEST MODE FOR CARRYING OUT THE INVENTION

In the following, the present invention will be explained in detail.

α-lactalbumin included as an active ingredient in an antiulcer agentaccording to the present invention can be prepared by the conventionalammonium sulfate precipitation method (for example, “New Edition ofModem Milk Engineering Handbook” written by Kinjirou Yukawa, DairyEngineering Extension Association, pages 120 to 122, 1975). In order toobtain it more easily, commercially available α-lactalbumin(manufactured by Sigma Co., Ltd., for example) can be utilized.

Moreover, α-lactalbumin can also be prepared by the iron chloride method(Journal of Food Science, volume 50, pages 1531 to 1536, 1985), theultrafiltration method (Japanese Unexamined Patent Application, FirstPublication No. Hei 5-268879), the ion exchange method (Japanese PatentNo. 2916047), or the like.

As is obvious from experiments described below, α-lactalbumin has littletoxicity, can be suitably used for oral administration, and can beprocessed by well known methods into tablets, capsules, troches, syrups,ampuled liquid medicines, granules, powders, or the like. Moreover,α-lactalbumin can be included in foods as an active ingredient toprepare foods having antiulcer properties as one embodiment of theantiulcer agents.

The antiulcer agents having various dosage forms described above can berespectively prepared by adding to α-lactalbumin a carrier which ispharmaceutically acceptable or can be used for foods. Specific examplesof the carrier include aqueous solvents such as distilled water,purified water, saline solutions, and the like; excipients such asL-glutamine, magnesium silicate, crystallzed cellulose, wheat starch,rice starch, D-sorbitol, dextran, dextrin, corn starch, lactose, potatostarch, powders of reduced maltose starch syrup, powders of cellulose,D-mannitol, aminoethyl sulfonate, fructose, xylitol, and the like;stabilizers such as sodium ascorbate, L-arginine, sodium arginate,benzoic acid, sodium edetate, glycerin, calcium gluconate, sodiumchondroitin sulfate, β-cyclodextrin, L-cystine, ethylparahydroxybenzoate, calcium pantothenate, potassium polyphosphate,sodium polyphosphate, methyl cellulose, and the like; pH buffersolutions containing respective pH regulators such as citric acid,sodium citrate, disodium citrate, sodium acetate, tartaric acid, sodiumhydroxide, sodium hydrogencarbonate, calcium lactate, sodiumhydrogenphosphate, disodium hydrogenphosphate, dipotassiumhydrogenphosphate, potassium dihydrogenphosphate, succinic acid, sodiumsuccinate, disodium succinate, or the like; antioxidants such asascorbic acid, tocopherol, tocopherol acetate, natural vitamin E, sodiumpyrosulfite, propyl gallate, and the like; lubricants such as sucrosefatty acid ester, lactose, calcium stearate, glycerine monostearate, andthe like; emulsifiers such as carageenan, glycerine fatty acid ester,sodium stearate, soybean lecithin, propylene glycol, yolk lecithin,sodium lauryl sulfate, sorbitan fatty acid ester, propylene glycol fattyacid ester, and the like; edulcorants such as hydrangea tea, isomerizedsaccharide, liquid sugar syrup, syrup, saccharin, white sugar, honey,dextrose, starch syrup, and the like; and coatings such as a gelatincapsule, and the like.

Although the dose of α-lactalbumin included in the antiulcer agent as anactive ingredient is determined in accordance with age, or the conditionof a patient, or the like, it is required to be orally administered inan amount of at least 10 mg per 1 kg of body weight, so as to exhibitantiulcer effects, as is obvious from the experiments described below.

In the antiulcer agent according to the present invention, the contentof α-lactalbumin included as an active ingredient for obtainingantiulcer effects is required to be at least 0.5 mg per 1 g of theantiulcer agent. Moreover, α-lactalbumin is more preferably included asan active ingredient in an amount of at least 1 mg per 1 g of theantiulcer agent.

Although the antiulcer agents according to the present invention havecurative or preventive effects on lesions in the gastrointestinal mucousmembrane, the degree of the effects depends on the causes of the ulcers,as is obvious from the experiments described below. For example, theantiulcer agent can exhibit superior curative or preventive effectsagainst stress-induced ulcers caused by stress, or alcohol-inducedulcers caused by alcohol, in comparison with ulcers induced by anonsteroidal anti-inflammatory drug (NSAID) such as indomethacin.

In the following, the present invention will be explained in detail byexperiments.

EXPERIMENT 1

The purpose of this experiment is to investigate antiulcer effects ofthe present invention in comparison with the prior art.

(1) Test Animals

Male Wistar rats weighing 230 to 270 g, 11 weeks old, (purchased fromJapan SLC CO., Ltd.) were randomly classified into five groups (eachconsisting of ten rats).

(2) Test Agents

Test agent 1: Distilled water for injection (blank test).

Test agent 2: An antiulcer agent in which an antiulcer substanceprepared in a manner identical to Example 1 described in Prior Art 1 isdissolved in distilled water to a concentration of 1 mg/ml.

Test agent 3: An antiulcer agent in which a commercially available wheyprotein (manufactured by Mirai Inc.) described in Prior Art 2 isdissolved in distilled water to a concentration of 1 mg/ml.

Test agent 4: An antiulcer agent in which a peptide hydrolysate preparedin a manner identical to Examples 2 and 3 described in Prior Art 3 anddescribed in Example 4 of the present invention is dissolved indistilled water to a concentration of 1 mg/ml.

Test agent 5: An antiulcer agent of the present invention, in which acommercially available α-lactalbumin (manufactured by Sigma Co., Ltd.)is dissolved in distilled water to a concentration of 1 mg/ml.

(3) Test Method

The experiment was carried out according to the method disclosed byRobert et al. (Gastroenterology, volume 77, pages 433 to 443, 1979).That is, rats were fasted for 24 hours and were orally administered witheach test agent at a dose of 10 mg/kg of an active ingredient in bodyweight. Test agent 1 for a blank test was orally administered to therats in an amount of 10 ml/kg body weight. After 30 minutes,hydrochloric acid and ethanol solution [hydrochloric acid and ethanolsolution (M=mol/dm³) prepared by mixing 500 mM of hydrogen chloride(HCl) solution and 75% ethanol solution at a volume ratio of 1.4)] wasorally administered to the rats at a dose of 5 ml/kg body weight.

After 1 hour, the rats were killed by ether inhalation, the stomach ofeach rat was taken out to the body surface, the pyloric part of thestomach was ligated, and then the stomach was removed. Then, 10 ml of 2%formalin solution was injected into the stomach from the cardiac partthereof, and the stomach was subsequently immersed in the formalinsolution for 10 minutes for fixation. Then, the curvatura ventriculimajor of the stomach fixed by formalin was cut to open, and the degreeof ulcers was measured by the following method.

That is, the total area of injured portions on the mucous membrane ofeach rat was measured, and then the degree of lesions on the mucousmembrane of each rat (score) was classified into six grades as shown inTable 1 in accordance with the total area of the injured portion.Moreover, the cumulative degree, which is the sum total of the degree oflesions on mucous membranes of ten rats in each group, was calculated asan index which shows the degree of ulcers in each group.

TABLE 1 Degree of lesions on mucous membrane Total area of injuredportions on (score) mucous membrane (mm²) 0 0 1  1˜20 2 21˜40 3 41˜60 461˜80 5  81˜100 6 over 100

(4) Test Results

Results of this experiment are shown in Table 2. As is clear from Table2, Test agent 5 of the present invention has superior antiulcer effectsin comparison with Test agent 2 to 4, each of which includes aconventional antiulcer agent.

Moreover, although other types of α-lactalbumin were also tested in thesame way, similar results were obtained.

TABLE 2 Number of test Cumulative degree of lesions on agent mucousmembrane 1 60 2 35 3 53 4 46 5 7

EXPERIMENT 2

This experiment was carried out in order to examine the acute toxicityof α-lactalbumin

(1) Test Animals

Male and Female CD (SD) rats, 6 weeks old, purchased from Japan SLC CO.,Ltd.) were respectively and randomly classified into three groups (eachconsisting of five rats) to be used for this experiment.

(2) Test Method

Commercially available α-lactalbumin (manufactured by Sigma Co., Ltd.)was dissolved in water for injection (manufactured by OtsukaPharmaceutical Co., Ltd.) to each of a concentration of 100 mg/ml and200 mg/ml, which were respectively and orally administered in an amountof 1 ml per 100 g of body weight (at each dose of 1000 mg and 2000 mgper 1 kg of rat body weight) to each rat of each group by single oralinstillation by means of a metal probe with a rounded tip, in order toexamine the acute toxicity. As a blank test, only water for injection(manufactured by Otsuka Pharmaceutical Co., Ltd.) was administered inthe same way to each rat of both groups of males and females.

(3) Test Results

Results of this experiment are shown in Table 3. As is clear from Table3, no deaths occurred in groups administered with α-lactalbumin at adose of 1000 mg/kg in body weight or 2000 mg/kg in body weight as wellas in the blank test (0 mg/kg). Therefore, it was determined that theLD₅₀ of α-lactalbumin was no less than 2000 mg/kg body weight,indicating that the toxicity of α-lactalbumin was extremely low.

Moreover, although other types of α-lactalbumin were also examined inthe same way, similar results were obtained.

TABLE 3 Dose Number of deaths/Total number (mg/kg) Male Female 0 0/5 0/51000 0/5 0/5 2000 0/5 0/5

EXPERIMENT 3

This experiment was carried out in order to examine the effective doseof α-lactalbumin.

(4) Test Animals

Male Wistar rats weighing 230 to 270 g, being 11 weeks old, (purchasedfrom Japan SLC CO., Ltd.) were randomly classified into four groups(each consisting of ten rats).

(2) Test Agents

As a test agent (an antiulcer agent including α-lactalbumin of thepresent invention as an active ingredient), commercially availableα-lactalbumin (manufactured by Sigma Co., Ltd.) was dissolved indistilled water to a concentration of 1 mg/ml. As a test agent for ablank test, distilled water was used.

(3) Test Method

This experiment was carried out in a manner identical to Example 1,except that α-lactalbumin included in the test agents as an activeingredient was respectively orally administered at a dose of 0 mg/kgbody weight (blank test), 1 mg/kg body weight, 10 mg/kg body weight, or100 mg/kg body weight.

(4) Test Results

Results of this experiment are shown in Table 4. As is clear from Table4, α-lactalbumin shows significant antiulcer effects by oraladministration at a dose of no less than 10 mg per 1 kg of body weight.From these results, it was determined that an effective dose for oraladministration of α-lactalbumin was at least 10 mg per 1 kg of bodyweight.

Moreover, although other types of α-lactalbumin were also examined inthe same way, similar results were obtained.

TABLE 4 Dose of active Cumulative degree of ingredient lesions on mucous(mg/kg) membrane 0 60 1 47 10 7 100 3

EXPERIMENT 4

This experiment was carried out for the purpose of examining therequired concentration of α-lactalbumin in an antiulcer agent of thepresent invention.

(1) Test Animals

Male Wistar rats weighing 230 to 270 g, 11 weeks old, (purchased fromJapan SLC CO., Ltd.) were randomly classified into six groups (eachconsisting of ten rats).

(2) Test Agents

As test agents (antiulcer agents including α-lactalbumin of the presentinvention as an active ingredient), commercially available α-lactalbumin(manufactured by Sigma Co., Ltd.) was dissolved in distilled water toeach concentration (content) of 0.25 mg/ml, 0.5 mg/ml, 1 mg/ml, and 5mg/ml. As a test agent for a blank test, distilled water was used.

(3) Test Method

This experiment was carried out in a manner identical to Example 1,except that α-lactalbumin included as an active ingredient in each testagent was respectively orally administered at a dose of 10 mg/kg bodyweight. The dose for the blank test was 0 mg/kg body weight.

(4) Test Results

Results of this experiment are shown in Table 5. As is clear from Table5, when the dose was fixed to the minimum effective dose as shown inExperiment 3 described above (in the ratio of 10 mg to 1 kg of bodyweight) and the concentration of α-lactalbumin is set to 0.25 mg/ml, 0.5mg/ml, 1 mg/ml, or 5 mg/ml, test agents including α-lactalbumin at aconcentration of no less than 0.5 mg/ml (0.5 mg/g when the specificgravity of distilled water is 1) show antiulcer effects. Moreover, testagents including α-lactalbumin at a concentration of no less than 1mg/ml (1 mg/g when the specific gravity of distilled water is 1) showsignificant antiulcer effects. From these test results, it wasidentified that the concentration of α-lactalbumin included in anantiulcer agent as an active ingredient is required to be no less than05 mg per 1 g.

Moreover, although other types of α-lactalbumin were also examined inthe same way, similar results were obtained.

TABLE 5 Dose of active Cumulative degree Concentration ingredient oflesions on (mg/ml) (mg/kg) mucous membrane 0 0 60 0.25 10 30 0.5 10 13 110 7 5 10 5 10 10 5

EXPERIMENT 5

This experiment was carried out for the purpose of examining whether theantiulcer effects of an antiulcer agent according to the presentinvention depend on the cause of the ulcers.

(1) Test Animals

Male Wistar rats weighing 230 to 270 g, 11 weeks old, (purchased fromJapan SLC CO., Ltd.) were randomly classified into six groups (eachconsisting of ten rats).

(2) Test Agents

As test agents (antiulcer agents including α-lactalbumin of the presentinvention as an active ingredient), commercially available α-lactalbumin(manufactured by Sigma Co., Ltd.) was dissolved in distilled water to aconcentration of 1 mg/ml to be used. As a test agent for a blank test,distilled water was used.

(3) Test Method

(a) Test Method 1 (Method for Induction of Alcohol-Induced Ulcers)

This experiment was carried out according to the method disclosed byRobert et al. (Gastroenterology, volume 77, pages 433 to 443, 1979) in amanner similar to Example 1. That is, rats fasted for 24 hours wereorally administered with each test agent at a dose of 10 mg/kg of anactive ingredient in body weight (test group number 1). The test agentfor a blank test was orally administered to rats in an amount of 10ml/kg in body weight (test group number 2). After 30 minutes,hydrochloric acid and ethanol solution [hydrochloric acid and ethanolsolution (M=mol/dm³) prepared by mixing 500 mM of hydrogen chloride(HCl) solution and 75% ethanol solution at a volume ratio of 1:4)] wasorally administered to the rats at a dose of 5 ml/kg body weight.

After 7 hours, the rats were killed by ether inhalation, the stomach ofeach rat was taken out to the body surface, the pyloric part of thestomach was ligated, and then the stomach was removed. Then, 10 ml of 2%formalin solution was injected into the stomach from cardiac partthereof, and the stomach was subsequently immersed in the formalinsolution for 10 minutes for fixation. Then, the curvatura ventriculimajor of the stomach fixed by formalin was cut to open, and the degreeof ulcers was measured in a manner identical to Example 1.

(b) Test Method 2 (Method for Induction of Stress-induced Ulcers)

This experiment was carried out in a manner identical to Method 1described above, except that ulcers were induced according to the methoddescribed by Takagi and Okabe (Japanese Journal of Pharmacology, volume18, pages 9 to 18, 1968). That is, rats fasted for 24 hours were orallyadministered with each test agent including at a dose of 10 mg/kg of anactive ingredient in body weight (test group number 3). The test agentfor a blank test was orally administered to rats in an amount of 10ml/kg body weight (test group number 4). After 30 minutes, each rat washeld in a stainless steel restrictive cage, and was left in a water tankat 23° C., standing and submerging to the depth of the bottom of thebreast xiphoid process of the rat.

After 7 hours, each rat was pulled up from the water tank, and thedegree of ulcers was measured in a manner identical to Method 1described above.

(c) Test Method 3 (Method for Induction of Ulcers Caused by aNonsteroidal Anti-inflammatory Drug)

This experiment was carried out in a manner identical to Method 1described above, except that ulcers were induced in accordance with themethod of Okabe, et al. (Japanese Journal of Pharmacology, volume 29,pages 670 to 673, 1968). That is, rats fasted for 24 hours were orallyadministered with the each test agent at a dose of 10 mg/kg of an activeingredient in body weight (test group number 5). The test agent for ablank test was orally administered to each rat in an amount of 10 ml/kgbody weight (test group number 6). After 30 minutes, indomethacin at adose of 30 mg/kg body weight, which is a representative nonsteroidalanti-inflammatory drug, was orally administered.

After 7 hours, the degree of ulcers was measured in a manner identicalto Method 1 described above.

(4) Test Results

Results of this experiment are shown in Table 6. As is clear from Table6, antiulcer actions of the antiulcer agent according to the presentinvention are recognized to be different in accordance with the causesof induction of ulcers, and antiulcer action on stress-induced ulcerscaused by stress (test group number 3) turned out to be superior to thaton ulcers caused by indomethacin which is a representative nonsteroidalanti-inflammatory drug (test group number 5).

Moreover, it is turned out that the antiulcer agent according to thepresent invention has a greater superior antiulcer action onalcohol-induced ulcers caused by alcohol (test group number 1) incomparison with antiulcer actions on the ulcers caused by indomethacin(test group number 5), and the antiulcer actions on alcohol-inducedulcers caused by alcohol (test group number 1) is superior to theantiulcer actions on stress-induced ulcers (test group number 3).

Results of blank tests in Methods 1 to 3 (test group numbers 2, 4, and6), in each of which the cumulative degree of lesions on mucousmembranes is the same value, show that antiulcer effects obtained inMethods 1 to 3 can be compared with one another.

Moreover, although other types of α-lactalbumin were also examined inthe same way, similar results were obtained.

TABLE 6 Cumulative degree of lesions Test group number on mucousmembrane 1 6 2 50 3 12 4 50 5 23 6 50

In the following, although the present invention will be explained inmore detail by way of Examples, the present invention is not limited tothe following Examples.

EXAMPLES Example 1

Tablets of an antiulcer agent including following compositions wereprepared in accordance with the following method.

Lactose (manufactured by Megre Co., Ltd.) 18.8 (%) Corn starch(manufactured by Ohoji Corn Starch Co., Ltd.) 67.9 Magnesium stearate(manufactured by Wako Pure Chemicals  1.4 Co., Ltd.) Calciumcarboxymethylcellulose  9.4 (manufactured by Dai-ichi Kogyo Seiyaku Co.,Ltd.) α-lactalbumin (manufactured by Sigma Co., Ltd.)  2.5

A mixture including α-lactalbumin, lactose, corn starch, and calciumcarboxymethylcellulose was uniformly kneaded with suitably addingsterilized purified water, and was dried at 50° C. for 3 hours to obtaina dry substance. Then, magnesium stearate was added into the drysubstance followed by mixing and forming of tablets in accordance with aconventional procedure using a machine for making tablets.

Example 2

An antiulcer syrup including the following components was prepared inaccordance with a conventional procedure.

Calcium carboxymethylcellulose  0.20 (%) (manufactured by Dai-ichi KogyoSeiyaku Co., Ltd.) Sodium citrate (manufactured by Wako Pure  0.18Chemicals Co., Ltd.) Citric acid (manufactured by Wako Pure ChemicalsCo., Ltd.)  0.22 Fructose glucose liquid sugar syrup 19.83 (manufacturedby Otsuka Pharmaceutical Co., Ltd.) Purified water (manufactured byOtsuka Pharmaceutical 78.57 Co., Ltd.) α-lactalbumin (manufactured bySigma Co., Ltd.)  1.00

Example 3

An antiulcer powdered medicine including the following components wasprepared in accordance with the following procedure.

Corn starch (manufactured by Ohoji Corn Starch Co., Ltd.) 57.5 (%)Crystallized cellulose (manufactured by Wako Pure Chemicals 37.5 Co.,Ltd.) α-lactalbumin (manufactured by Sigma Co., Ltd.)  5.0

Materials described above were mixed uniformly and were prepared intopowers in accordance with a conventional procedure.

INDUSTRIAL APPLICABILITY

As described above in detail, the present invention relates to antiulceragents including α-lactalbumin as an active ingredient, and can achievethe following effects.

(1) Because the antiulcer agents produce few side effects, they can beadministered for a long time.

(2) Because α-lactalbumin has heat-resisting properties, and haswater-soluble properties which causes stability in a solution, it isstable as a drug.

(3) Because the antiulcer agents can be orally administered, they can beeasily administered for general purposes in comparison with injection.

(4) Because α-lactalbumin can be prepared from relatively inexpensiveraw materials such as milk or the like, it can be prepared on a largescale.

What is claimed is:
 1. A method for treatment of ulcers, comprising thestep of administering an antiulcer agent consisting of α-lactalbumin asthe sole antiulcer agent to a subject in need thereof.
 2. A method oftreating ulcers comprising administering at least 10 mg per kilogram ofbody weight per dose of α-lactalbumin as the sole active ingredient to asubject in need thereof.
 3. A method of treating ulcers comprisingadministering a composition consisting of at least 10 mg per kilogram ofbody weight per dose of α-lactalbumin as the sole active ingredienttogether with a pharmaceutically accepted carrier to a subject in needthereof.
 4. A method of treating ulcers according to claim 2, whereinthe dose is at least 100 mg per kilogram of body weight.
 5. The methodof treating ulcers according to claim 3, wherein the compositioncontains at least 1 mg of α-lactalbumin per 1 g of composition.
 6. Themethod of treating ulcers according to claim 3, wherein the compositioncontains at least 5 mg of α-lactalbumin per 1 g of composition.
 7. Themethod of treating ulcers according to claim 3, wherein the compositioncontains at least 10 mg of α-lactalbumin per 1 g of composition.
 8. Themethod of treating ulcers according to claim 3, wherein the compositioncontains at least 25 mg of α-lactalbumin per 1 g of composition.
 9. Themethod of treating ulcers according to claim 3, wherein the compositioncontains at least 50 mg of α-lactalbumin per 1 g of composition.
 10. Themethod of treating ulcers according to claim 3, wherein, in addition toα-lactalbumin, the composition includes at least one or more of anaqueous solvent, an excipient, a stabilizer, a pH buffer solutioncontaining pH buffers, an antioxidant, a lubricant, an emulsifier, anedulcorant or a coating.
 11. The method of treating ulcers according toclaim 3, wherein the composition has a form of a tablet, capsule,troche, syrup, ampuled liquid medicine, granule or a powder.
 12. Amethod of treating ulcers according to claim 2 wherein the ulcers arestress-induced ulcers, alcohol-induced ulcers, or ulcers caused by anonsteroidal anti-inflammatory drug.
 13. A method of treating ulcersaccording to claim 3 wherein the ulcers are stress-induced ulcers,alcohol-induced ulcers, or ulcers caused by a nonsteroidalanti-inflammatory drug.
 14. A method of treating ulcers according toclaim 4 wherein the ulcers are stress-induced ulcers, alcohol-inducedulcers, or ulcers caused by a nonsteroidal anti-inflammatory drug.